Prostate cancer is a clinically variable disease – some patients do well, while others do very poorly – and recent studies have shown clear molecular subtypes of prostate cancer that may explain this variability. Some subtypes of prostate cancer have underlying defects in repairing their DNA, making them potentially sensitive to therapies that exploit this deficiency. Dr. Barbieri [MetLife Foundation Clinical Investigator] is a surgeon scientist whose overall goal is to translate our understanding of the molecular basis of prostate cancer into near term benefits for patients. He will investigate the response to novel therapies for prostate cancer in patients undergoing surgical therapy for early stage disease, and define the genomic alterations that predict which cancers will be sensitive to these agents. Defining the response and the predictors of new agents in early, untreated prostate cancer will change the paradigm of how we treat men with the disease, allowing a precision medicine approach.

Dr. Owens focuses on heat shock proteins (HSPs) and their “master regulator” called heat shock transcription factor 1 (HSF1). The transformation and growth of cancers causes a wide array of cellular stresses including metabolic changes, genomic instability, and protein misfolding that would halt the growth of a normal cell. Tumor cells, however, depend on cellular stress response machinery, like HSPs, for their survival. HSF1 is critical to tumor development and progression, and HSF1 activity is strongly correlated with poor prognosis in many common cancers. For decades, efforts to develop cancer therapies targeting HSPs have failed. Dr. Owens aims to understand how HSPs and HSF1 interact to regulate activity, and how this regulation is co-opted to promote tumor growth and progression.

Prostate cancer is the second leading cause of cancer death in men in the United States. Remarkably, work over the past decade has demonstrated that even the worst prostate cancers are dependent on the same signaling pathways that govern normal prostate behavior. Dr. Shoag’s objective is to identify drugs that have activity against the normal prostate and can be used to understand and treat prostate cancer. Dr. Shoag will apply novel statistical and machine learning approaches on large scale clinical data to discover new therapies and pathways important in prostate cancer. He will then test these therapies in genetically engineered and patient-derived prostate cancer models. Identifying active drugs against prostate cancer that are already FDA-approved or have been previously studied in clinical trials for other cancers can aid in understanding prostate cancer biology and can rapidly benefit patients with advanced disease.